Journal
HYPERTENSION
Volume 58, Issue 4, Pages 650-U280Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.111.170472
Keywords
oxidative stress; reactive oxygen species; hydrogen peroxide; renal autoregulation; hypertension
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-036079, DK-049870, HL-089583]
- National Heart, Lung and Blood Institute [HL-68686]
- George E. Schreiner Chair of Nephrology
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Reactive oxygen species enhance or impair autoregulation. Because superoxide is a vasoconstrictor, we tested the hypothesis that stretch generates superoxide that mediates myogenic responses. Increasing perfusion pressure of mouse isolated perfused renal afferent arterioles from 40 to 80 mm Hg reduced their diameter by 13.3 +/- 1.8% (P<0.001) and increased reactive oxygen species (ethidium: dihydroethidium fluorescence) by 9.8 +/- 2.3% (P<0.05). Stretch-induced fluorescence was reduced significantly (P<0.05) by incubation with Tempol (3.7 +/- 0.8%), pegylated superoxide dismutase (3.2 +/- 1.0%), or apocynin (3.5 +/- 0.9%) but not by pegylated catalase, L-nitroarginine methylester, or Ca2+-free medium, relating it to Ca2+-independent vascular superoxide. Compared with vehicle, basal tone and myogenic contractions were reduced significantly (P<0.05) by pegylated superoxide dismutase (5.4 +/- 0.8), Tempol (4.1 +/- 1.0%), apocynin (1.0 +/- 1.3%), and diphenyleneiodinium (3.9 +/- 0.9%) but not by pegylated catalase (10.1 +/- 1.6%). L-Nitroarginine methylester enhanced basal tone, but neither it (15.8 +/- 3.3%) nor endothelial NO synthase knockout (10.2 +/- 1.8%) significantly changed myogenic contractions. Tempol had no further effect after superoxide dismutase but remained effective after catalase. H2O2 >50 mu mol/L caused contractions but at 25 mu mol/L inhibited myogenic responses (7.4 +/- 0.8%; P<0.01). In conclusion, increasing the pressure within afferent arterioles led to Ca2+-independent increased vascular superoxide production from nicotinamide adenine dinucleotide phosphate oxidase, which enhanced myogenic contractions largely independent of NO, whereas H2O2 impaired pressure-induced contractions but was not implicated in the normal myogenic response. (Hypertension. 2011;58:650-656.)
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